Isolation of rare cells from peripheral blood is a difficult and tedious step in the diagnosis and treatment of cancer. Examples include leukocytes, which are of interest in leukemia, circulating endothelial cells, which can serve as a surrogate marker for solid tumor treatment, and circulating cancer cells, which may provide a tool for diagnosis and prognosis. In most patients, each of these cell types is outnumbered by red blood cells by a factor of at least 1000. Therefore, isolation of these cells from a sample of whole blood is the required first step of many clinical and basic research assays. We recently described a microfluidic device that takes advantage of plasma skimming and leukocyte margination - intrinsic features of blood flow in the microcirculation - to enrich nucleated cells such as leukocytes directly from whole blood. It consists of a simple network of rectangular microchannels manufactured using standard photolithography and silicone molding techniques, and requires only pressure-driven flow to operate. Its initial channel is designed to enhance lateral migration of spherical cells, which, once near the wall are easily extracted through small extraction channels. In our preliminary design, a single pass through the device produces 34-fold enrichment of the leukocyte-to-erythrocyte ratio. We propose to further develop the microfluidics to provide simple, efficient and inexpensive technology for use as an initial stage in lab-on-a-chip analyses. Its integration into microanalytical devices that require rare cell enrichment will provide less expensive, more reliable, clinical assays that are also convenient and portable for point-of-care testing. Specifically, we will maximize the purity and efficiency of nucleated blood cell isolation and compare the performance with traditional separation techniques. When fully-developed, this technology will be a necessary and integral component of any microfluidic device analyzing nucleated blood cell populations by eliminating the need for preliminary blood processing steps. [unreadable] [unreadable] [unreadable]